Cardio-Respiratory Interaction: Contribution in Syncope

呼吸系统和心血管调节系统有共同的内稳态目标，然而，动态不适当的调整可能会导致另一个系统的不良后果。我们的一般假设是动态的心肺相互作用在晕厥的发生中起重要作用。在晕厥之前的呼吸模式的改变已经有几年的轶事报道。来自最近研究的证据支持这些观察结果。我们假设了以下一系列事件：动脉二氧化碳分压（PCO2）的短暂紊乱，由灌注振荡引起，触发通气调节。这些振荡在直立时振幅增加。在那些对二氧化碳化学敏感性过高的人群中，通气量调整导致通气量变异性增加。由此产生的呼吸急促和低碳酸血症，通过脑血流的改变，化学反射介导的交感神经戒断，或改变的胸内力学，触发血流动力学不稳定，虚脱和晕厥。我们将验证对化学刺激变化的过度敏感性是否会导致晕厥前的通气改变，量化通气改变的两种后果，化学驱动和胸内力学，单独或共同在晕厥发生中的作用。我们将在人体中使用头向上倾斜的方法，以1)验证出现晕厥症状的受试者对二氧化碳扰动的动态通气反应是否比没有出现晕厥症状的受试者夸张，2)量化在没有呼吸变化的情况下动脉二氧化碳分压（PCO2）降低对脑血管收缩和晕厥的影响，以及3)量化PCO2缓冲变化对呼吸改变、呼吸急促、脑血管收缩和晕厥。我们的研究将提供结果来回答这些重要的问题；是什么原因导致晕厥前经常观察到通气变异性增加？，在通气保持不变的情况下，二氧化碳分压降低对晕厥有什么影响？在二氧化碳分压不变的情况下，换气对晕厥有什么影响？总的来说，这些结果将为进一步了解晕厥的机制创造知识，晕厥使人衰弱，有时甚至是危险的情况，影响了10%到15%的年轻人和成年人。

Respiratory and cardiovascular regulatory systems share goals of homeostasis, however, dynamically inappropriate adjustments in one may precipitate undesirable consequences in other. Our general hypothesis is that dynamic cardio-respiratory interaction contributes importantly in genesis of syncope. Changes in respiratory patterns preceding syncope have been anecdotally reported for several years. Evidence from recent studies support these observations. We hypothesize the following chain of events: transient disturbances in arterial partial pressure of carbon dioxide (PCO2), precipitated by oscillations in perfusion, trigger ventilatory adjustments. These oscillations increase in amplitude during orthostasis. The ventilatory adjustments, in those with exaggerated chemical sensitivity to carbon dioxide, leads to increased ventilatory variability. The resulting periods of hyperpnea and hypocapnia, through changes, either or collectively, in cerebral blood flow, chemoreflex mediated sympathetic withdrawal, or altered intrathoracic mechanics, trigger hemodynamic instability, collapse and syncope. We will, verify whether exaggerated sensitivity to changes in chemical stimuli produces altered ventilation preceding syncope, quantify the role of two consequences of altered ventilation, chemical drive and intrathoracic mechanics, independently and together, in genesis of syncope. We will use head up tilt in humans, to 1) verify whether the dynamic ventilatory response to carbon dioxide perturbations in subjects who develop syncopal symptoms is exaggerated than those that do not, 2) quantify the effects of decrease in arterial partial pressure of carbon dioxide (PCO2), in the absence of changes in respiration, on cerebral vasoconstriction and syncope, and 3) quantify the effects of buffered changes in PCO2, on altered breathing, hyperpnea, cerebral vasoconstriction and syncope. Our study will provide results to answer these important questions; what causes the often observed increased ventilatory variability before syncope?, what are the effects on syncope of decreases in PCO2, while ventilation remains unchanged? what are the effects on syncope of changes in ventilation, while PCO2 remains unchanged? Collectively, these results will create knowledge to further understand the mechanisms of the debilitating and sometimes dangerous condition of syncope that affects upwards of 10 to 15 percent of young and adult population.